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Copper-nitrite complexes release nitric oxide and selectively induce oral precancer and cancer cell apoptosis

Yen-Yun Wang1, Pang-Yu Chen2, Naorem Jemes Meitei3

  • 1School of Dentistry, College of Dental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.

Journal of Inorganic Biochemistry
|January 24, 2025
PubMed

Insights

Copper-nitrite complexes show promise for treating oral precancer and cancer. L1Cu(NO2) selectively kills cancer cells by halting cell cycle progression and inducing apoptosis, suggesting targeted therapy potential.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Nitric oxide (NO) is a critical signaling molecule involved in numerous physiological processes.
  • Dysregulated NO signaling is implicated in various diseases, including cardiovascular conditions, diabetes, and cancers.
  • Oral precancer and cancer represent significant global health challenges requiring novel therapeutic strategies.

Purpose of the Study:

  • To investigate the therapeutic potential of copper-nitrite complexes in oral precancer and cancer treatment.
  • To evaluate the ability of novel copper-nitrite complexes (L1Cu(NO2) and L2Cu(NO2)) to release nitric oxide (NO) within cells.
  • To assess the selective cytotoxicity and underlying mechanisms of these complexes in oral cancer cells.

Main Methods:

  • Synthesis and characterization of copper-nitrite complexes, L1Cu(NO2) and L2Cu(NO2).
  • In vitro assessment of NO release from the complexes within cancer cells.
  • Evaluation of selective cytotoxicity against oral precancer and cancer cell lines.
  • Analysis of cell cycle progression (G0/G1 arrest) and apoptosis induction.
  • Measurement of p-PRAS40 (proline-rich Akt substrate of 40 kDa) expression levels.

Main Results:

  • Copper-nitrite complexes effectively released NO into oral cancer cells.
  • Both L1Cu(NO2) and L2Cu(NO2) demonstrated selective cytotoxicity towards oral precancer and cancer cells.
  • L1Cu(NO2) significantly inhibited oral cancer cell proliferation by inducing G0/G1 phase cell cycle arrest.
  • L1Cu(NO2) promoted cancer cell apoptosis and upregulated the expression of p-PRAS40.

Conclusions:

  • Copper-nitrite complexes, particularly L1Cu(NO2), exhibit significant therapeutic potential for oral precancer and cancer.
  • The mechanism involves selective NO release, leading to cell cycle arrest, apoptosis, and modulation of key signaling pathways.
  • These findings support the development of L1Cu(NO2) as a targeted therapeutic agent for oral oncology.
Keywords:
ApoptosisCell cycleCopper-nitrite complexNitric oxideOral cancerPRAS40

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